title: Intracellular ATP concentration contributes to the cytotoxic and cytoprotective effects of adenosine.
abstract: Extracellular adenosine (ADE) interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.
authors.affiliation: Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China ; Department of Urology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Shujue
authors.initials: S
authors.lastname: Li
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Li
authors.forename: Haiping
authors.initials: H
authors.lastname: Guo
authors.forename: Shouting
authors.initials: S
authors.lastname: Liu
authors.forename: Hongbiao
authors.initials: H
authors.lastname: Huang
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.forename: Changshan
authors.initials: C
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Tang
authors.forename: Jinbao
authors.initials: J
authors.lastname: Liu
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D003600:Cytosol / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D003603:Cytotoxins; D018047:Receptors, Purinergic P1; D000255:Adenosine Triphosphate; D000241:Adenosine